Pathways to the new biology: Elissa Chesler, Ph.D.

Assistant Professor Elissa Chesler, Ph.D., began her scientific career in psychology and behavioral neuroscience. The fields are known for their contributions to statistics, needed to meet the challenge of characterizing the vagaries of human behavior in disciplined and empirical ways. But Chesler was most skeptical of the very methods by which these behaviors were being studied.

“The DSM (the manual that defines psychiatric diseases and mental health disorders for diagnoses) uses observed behaviors but doesn’t account for the underlying biological causes,” says Chesler. “We need a better, more precise way to define complex behaviors and develop coherent categories for them based on the underlying biology.”

Chesler’s drive to achieve the task took shape when she was an M.D./Ph.D. student at the University of Illinois. She was able to complete her Ph.D. work in the psychology department, where she started her work on neuroendocrine effects on brain and behavior.

“It was important work, but in the end I didn’t find it all that interesting—there were never enough numbers. I finished my degree with a behavioral geneticist. It was there where I wanted to go beyond simple mapping of the genetic influences on behavior and initiated my first large scale data mining.When I quantified all the measures of a single behavior ever taken in my advisor’s lab, I found the data were more influenced by who did the experiment than the genetics of the mice he or she used. We also started devising new quantitative methods to map the genetic modifiers of behavior, but from these studies I found that both the resources and methods lacked precision. I’ve been working since then to improve both the methods and the mouse populations used.”

Chesler became so “fired up” about this goal that medical school had to wait. She went to do her post-doctoral work at the University of Tennessee, where she made use of mouse strains to find genes that influence behavior and gene expression in the brain. This work was an early example of a new synthesis of systems biology to genetics, now called “systems genetics”.She also became involved early on with the Collaborative Cross (CC) mouse project, which sought to develop better strains of mice for more precise complex trait research. This massive endeavor needed a home, and she was instrumental in securing one in the Department of Energy’s Oak Ridge National Laboratory where went on to to lead the initial production and characterization the effort, which has now yielded useful research populations.

Chesler’s current work involves analyzing massive data sets to try to tease apart what genes and gene networks are associated with behaviors and to effectively correlate mouse behavior in labs with human behaviors. “I never did go back to med school,” she says. “I feel what I’m doing now will help far more people than I could have helped as a doctor. Today, each patient presenting with a serious mental health problem is an experiment with the patient being the lone subject. We don’t know the basis of their problem, and we don’t know which therapy will be most effective. I’m working to provide patients with that vital information up front.”